Skeletal characterization in a patient with Hajdu-Cheney syndrome undergoing total knee arthroplasty.
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ABSTRACT:
SUBMITTER: von Vopelius E
PROVIDER: S-EPMC8387270 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hajdu Cheney Syndrome (HCS), Orpha 955, is a rare disease characterized by acroosteolysis, severe osteoporosis, short stature, specific craniofacial features, wormian bones, neurological symptoms, cardiovascular defects and polycystic kidneys. HCS is rare and is inherited as autosomal dominant although many sporadic cases have been reported. HCS is associated with mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the creation of a truncated and stable NOTCH2 protein with enhanced NOTCH2 signaling activity. Although the number of cases with NOTCH2 mutations reported are limited, it would seem that the diagnosis of HCS can be established by sequence analysis of exon 34 of NOTCH2. Notch receptors are single-pass transmembrane proteins that determine cell fate, and play a critical role in skeletal development and homeostasis. Dysregulation of Notch signaling is associated with skeletal developmental disorders. There is limited information about the mechanisms of the bone loss and acroosteolysis in HCS making decisions regarding therapeutic intervention difficult. Bone antiresorptive and anabolic agents have been tried to treat the osteoporosis, but their benefit has not been established. In conclusion, Notch regulates skeletal development and bone remodeling, and gain-of-function mutations of NOTCH2 are associated with HCS.
| S-EPMC4269900 | biostudies-literature
Project description:Hajdu-Cheney Syndrome (HCS) is a rare hereditary bone metabolism disorder characterized by acro-osteolysis, short stature, craniofacial changes, periodontitis and premature tooth loss. Extensive search of the current literature revealed no reports of implant placement in patients with HCS.A 22-year old woman with osteoporosis, generalized advanced chronic periodontitis and premature tooth loss was referred to the Postgraduate Clinic of Periodontology, University of Athens-Greece. The patient was diagnosed in 2001 with HCS. The patient received non-surgical periodontal treatment and several teeth were extracted due to extensive alveolar bone loss. After careful consideration of the possible implications deriving from the patient's condition and having taken her young age into account, initially, a dental implant was placed in the upper right first premolar region. Specific protocols such as longer healing periods were implemented, so five years after placement and successful osseointegration of this implant, four additional dental implants were placed in the posterior regions of the maxilla and the mandible. Prosthetic rehabilitation followed 6 months after implant placement. Upon completion of periodontal treatment, the patient was enrolled in a periodontal maintenance program.Clinical and radiographic examination of the patient during the periodontal maintenance program after implant placement revealed no abnormalities in the implant region.Patients with HCS suffer from periodontitis, bone destruction and premature tooth loss. This case indicates the successful osseointegration of dental implants in patients with HCS. However, further research is required in order to determine the predictability of dental implant placement in those patients.
| S-EPMC5093869 | biostudies-other
Project description:UnlabelledThe Hajdu-Cheney syndrome is a very rare disease that affects several organ system, leading to severe osteoporosis and other abnormalities. We describe clinical and genetic findings of nine patients with this disease.IntroductionThe Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts, and other abnormalities. Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS.MethodsNine patients with typical presentations of HCS took part in this study: five affected patients from two small families and four sporadic cases. Peripheral blood DNA was obtained and exome sequencing performed in one affected individual per family and in all four sporadic cases. Sanger sequencing confirmed mutations in all patients.ResultsOne of the identified mutations was introduced in a plasmid encoding NOTCH2. Wild-type and mutant NOTCH2 were transiently expressed in HEK293 cells to assess intracellular localization after ligand activation. Deleterious heterozygous mutations in the last NOTCH2 exon were identified in all patients; five of the six mutations were novel.ConclusionConsistent with previous reports, all mutations are predicted to result in a loss of the proline/glutamic acid/serine/threonine sequence, which harbors signals for degradation, therefore suggesting activating mutations. One of the six mutations furthermore predicted disruption of the second nuclear localization signal of NOTCH2, but the mutant revealed normal nuclear localization after transfection, which is consistent with the proposed gain-of-function mechanism as the cause of this autosomal dominant disease. Our findings confirm that heterozygous NOTCH2 mutations are the cause of HCS and expand the mutational spectrum of this disorder.
| S-EPMC4037401 | biostudies-literature
Project description:Hajdu-Cheney syndrome (HCS) is a rare genetic disease that causes acroosteolysis and generalized osteoporosis, accompanied by a series of developmental skeletal disorders and multiple clinical and radiological manifestations. It has an autosomal dominant inheritance, although there are several sporadic non-hereditary cases. The gene that has been associated with Hajdu-Cheney syndrome is NOTCH2. The described phenotype and clinical signs and symptoms are many, varied, and evolve over time. As few as 50 cases of this disease, for which there is currently no curative treatment, have been reported to date. The main objective of this systematic review was to evaluate the results obtained in research regarding Hajdu-Cheney Syndrome. The findings are reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and were registered on the web PROSPERO under the registration number CRD42020164377. A bibliographic search was carried out using the online databases Orphanet, PubMed, and Scielo; articles from other open access sources were also considered. Finally, 76 articles were included, and after their analysis, we have obtained a series of hypotheses as results that will support further studies on this matter.
| S-EPMC7504254 | biostudies-literature
Project description:This paper describes the case of a 54-year-old woman diagnosed with Hajdu-Cheney syndrome, who presents with characteristic craniofacial dysmorphia, short stature, premature loss of teeth, developmental skeletal disorders, fibrocystic mastopathy, bilateral hearing loss and an intermittent mild neutropenia. The patient received treatment with bisphosphonates and was awaiting evaluation for surgical arthroplasty of both hips when she suffered a motor vehicle accident, which led to a rapid progression in her disease by increasing her degree of dependence for most activities of daily living. The clinical presentation and radiologic findings seen in this case confirm the three main features of the syndrome: phenotypic variability, an age-dependent progression and the presence of generalized osteoporosis and acroosteolysis of distal phalanges. The main objective of the manuscript is to describe a new case of a patient diagnosed with Hajdu-Cheney syndrome. Due to the low prevalence of the syndrome and the small number of cases reported in the scientific literature, obtaining a complete description and a global perspective of the disease is complex.
| S-EPMC8947164 | biostudies-literature
Project description:Hajdu-Cheney syndrome is a rare genetic disease. Its main features include phenotypic variability, age-dependent progression and the presence of acroosteolysis of the distal phalanges and generalized osteoporosis, which have significant disabling potential. Currently, there is no effective curative treatment, so nursing care is essential to ensure the maintenance of the quality of life of these patients. The main objective of this study was to establish a specific standardized nursing care plan using the NANDA-NIC-NOC taxonomy. The application of a care plan as such would improve the quality of life of patients affected by this rare disease, will contribute to increasing healthcare professionals' knowledge on this matter and will support future studies on this disease.
| S-EPMC9223558 | biostudies-literature
Project description:Hajdu-Cheney Syndrome (HSC) is a rare multisystem disease in which the phenotype involves acro-osteolysis, severe osteoporosis, short stature, wormian bones, facial dysmorphism, central neurological abnormalities, cardiovascular defects, and polycystic kidneys. We describe an infant with severe manifestations of HCS in whom congenital glaucoma was a significant early feature, which has not been reported to date. HCS cases reported to date have involved truncating mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the development of a truncated and stable NOTCH2 protein which upregluates notch signaling. We describe a hitherto undescribed missense mutation that is predicted to be pathogenic, with functional characterization remaining to be performed. Serpentine fibula-polycystic kidney syndrome (SFPKS) is allelic to HCS and commonly associated with missense NOTCH2 mutations. Our patient provides new ophthalmological manifestations of HCS and provides insight into the potential role of notch signaling in the anterior chamber development.
| S-EPMC6215579 | biostudies-literature
Project description:To systematically review the evidence for using anabolic-androgenic steroids (AAS) to aid rehabilitation following total knee replacement (TKR).Systematic review of all clinical study designs.MEDLINE, EMBASE, AMED, CINAHL and the Cochrane Library were searched from inception to August 2012.All clinical study designs without language or patient demographic limits.All functional, physiological and administrative outcomes as well as reporting of adverse events.Only two small randomised controlled trials satisfied the inclusion criteria. Statistically significant improvements were reported in the AAS group for quadriceps strength at 3 (p=0.02), 6 (p=0.01) and 12 (p=0.02) months, Functional Independence Measure score at 35 days (p=<0.05) and Knee Society Score at 6 weeks (p=0.02), 6 months (p=0.04) and 12 months (p=0.03). However, differences in hamstring strength, bone mineral density, sit-to-stand testing, walking speed, length of hospital stay and need for further inpatient rehabilitation did not reach statistical significance. There were no reported adverse events.There is insufficient evidence to recommend routine administration of AAS to patients undergoing TKR. However, pilot data suggest that AAS can be administered safely and may improve important postoperative outcome measures. This justifies a randomised trial sufficiently powered to identify between-group differences likely to be of clinical significance.
| S-EPMC3468811 | biostudies-literature
Project description:Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasty (TKA). Current surgical and pharmacologic treatment options are limited. Therefore, an in vitro model for joint myofibroblastogenesis is valuable to investigate the arthrofibrotic process and identify diagnostic biomarkers and treatment options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissue from knees of four patients undergoing primary TKA for osteoarthritis and characterized primary outgrowth cells from these tissues in the absence and presence of transforming growth factor beta 1 (TGFβ1), a pro-myofibroblastic cytokine. Light microscopy of knee outgrowth cells revealed spindle-shaped cells while immunofluorescence (IF) established staining for the fibroblast-specific antigen TE-7 and Vimentin, which are characteristics of fibroblasts. These fibroblasts differentiate readily into myofibroblasts as highlighted by enhanced alpha smooth muscle actin (ACTA2) mRNA and protein expression and increased collagen mRNA (i.e., collagen type 1 (COL1A1) and collagen type 3 (COL3A1)) expression and collagenous matrix deposition in the presence of TGFβ1. Of note, these studies also revealed that knee-derived fibroblasts are more sensitive to TGFβ1-mediated myofibroblastogenesis than adipose-derived mesenchymal stem cells. Importantly, while outgrowth fibroblasts isolated from four patients and three anatomical regions exhibit similar gene expression profiles, these knee fibroblasts form a unique gene expression cluster within the fibroblast niche as revealed by RNA-sequencing analysis. In conclusion, our study provides a fibroblast/myofibroblast model of outgrowth knee cells derived from patients undergoing primary TKA that can be employed to assess myofibroblast-related processes and test novel pharmacological strategies in vitro for arthrofibrosis.
2022-03-01 | GSE185333 | GEO
Project description:Osteoarthritis is a joint disease characterized by cartilage degradation, altered gene expression and inflammation. NOTCH1 and NOTCH2 receptors and the JAGGED1 ligand regulate chondrocyte biology; however, the contribution of Notch signaling to osteoarthritis is controversial. Hajdu Cheney Syndrome (HCS) is a rare genetic disorder affecting the skeleton and associated with NOTCH2 mutations that lead to NOTCH2 gain-of-function. A murine model of the disease (Notch2tm1.1Ecan) was used to test whether the HCS mutation increases the susceptibility to osteoarthritis. The knee of three-month-old Notch2tm1.1Ecan male mice and control sex-matched littermates was destabilized by resection of the medial meniscotibial ligament, and changes in the joint analyzed two months thereafter. Expression of Notch target genes was increased in the femoral heads of Notch2tm1.1Ecan mice, documenting Notch signal activation. Periarticular bone and cartilage structures were unaffected in Notch2tm1.1Ecan mutants subjected to sham surgery, indicating that NOTCH2 gain-of-function had no discernible impact on joint structure under basal conditions. However, destabilization of the medial meniscus increased osteophyte volume and thickened subchondral bone in Notch2tm1.1Ecan mice compared to wild type littermates. Moreover, destabilized Notch2tm1.1Ecan mutants exhibited histological signs of moderate to severe cartilage degeneration, demonstrating joint sensitization to the development of osteoarthritis. Chondrocyte cultures from Notch2tm1.1Ecan mutants expressed increased Il6 mRNA levels following exposure to JAGGED1, possibly explaining the susceptibility of Notch2tm1.1Ecan mice to osteoarthritis. In conclusion, Notch2tm1.1Ecan mutants are sensitized to the development of osteoarthritis in destabilized joints and NOTCH2 activation may play a role in the pathogenesis of the disease.
| S-EPMC6083868 | biostudies-literature